In the past, antibiotics have been used to treat various infections. The work of Selman Waksman in the introduction and production of Streptomycetes, and Dr. Fleming's discovery of penicillin, as well as the work of numerous others in the field of antibiotics, are well known. Over the years, there have been additions and chemical modifications to the “basic” antibiotics in attempts to make them more powerful, or to treat people allergic to these antibiotics.
However, as more antibiotics have been prescribed or used at an ever-increasing rate for a variety of illnesses, increasing numbers of bacteria have developed a resistance to antibiotics. Larger doses of stronger antibiotics are now being used to treat ever more resistant strains of bacteria. Consequently, multiple antibiotic resistant bacteria have been developed and some hospital-acquired infections with Gram-positive bacteria have already become untreatable. The use of more antibiotics and the number of bacteria showing resistance has led to increases in the amount of time that the antibiotics need to be used. Broad, non-specific antibiotics, some of which have detrimental effects on the patient, are now being used more frequently. Additionally, the number of people showing allergic reactions to antibiotics appears to be increasing.
Consequently, other efforts have been sought to first identify and then kill bacteria.
Attempts have been made to treat bacterial diseases with the use of bacteriophages. These are a heterogeneous group of viruses that infect bacteria that were first discovered in the early part of the 20th Century (d'Herelle, F., The bacteriophage. Its role in immunity, translated by Smith, G. H., Williams & Wilkins Co., Baltimore (1922)). Bacteriophages presently are widely used in scientific research, such as in molecular biology (e.g. as genetic vectors) and in medical diagnostics (e.g. phage typing of bacteria). Insofar as phages naturally infect and kill bacteria, it traditionally was suggested that they could be utilized in medical therapeutics, because bacteria are a major cause of disease.
Indeed, potential therapeutic uses of phage in experimental systems have been reported extensively in the literature.
For example, U.S. Pat. No. 5,688,501 (Merril, et al.) discloses a method for treating an infectious bacterial disease with lytic or non-lytic bacteriophages that are specific for particular bacteria.
Also, U.S. Pat. No. 4,957,686 (Norris) discloses a procedure of improved dental hygiene which comprises introducing into the mouth bacteriophages parasitic to bacteria which possess the property of readily adhering to the salivary pellicle.
Despite the recognized value and importance of new antimicrobial therapies, the potential of phage therapy has not been accomplished in any practical sense that is used in modem therapeutics, nor have methods, compositions, or other uses been defined for nontoxic and efficacious therapies of this type with practical and effective delivery. In particular for efficient prevention and treatment of infections related to E. coli, such as diarrhea diseases.
In fact, E. coli is an extremely well-investigated bacterium, with two completely sequenced members, the non-pathogenic strain K-12 (Blattner, F. R., et al., 1997 Science 277, 1453–1474) and the pathogenic strain 0157:H7 (Perna, N. T. et al., 2001, Nature 409, 529–533; Hayaslis et al., 2001, DNA Research 8, 11–22) which resembles enteropathogenic E. coli (EPEC) strains.
Although, two E. coli phages (lambda and T4) are the most carefully characterized biological systems (Karam, J. D., 1994, Molecular biology of bacteriophage T4. ASM Press, Washington, D.C.), there still exists a need to develop new and useful phage therapeutics which can be used to prevent or to treat infectious disorders caused by such bacterial microorganisms, such as E. coli serotypes associated with diarrhea of children and the traveler.
There also exists a need to develop compositions including phage therapeutics in acceptable vehicles that can be administered to subjects infected with bacterial microorganisms.
Finally, there exists a need to develop a bacteriophage preparation that is virulent and non-toxic thereby rendering it useful in treating bacterial infections related to pathogenic E. coli or Salmonella. 